1. Field of the Invention
The present invention relates to a recombinant fowlpox virus and vaccine containing said virus that is useful in protecting poultry against avian reticuloendotheliosis retrovirus-induced diseases.
2. Description of Related Art
The reticuloendotheliosis viruses (REVs) are a group of oncogenic and immunodepressive type C avian retroviruses (52). They are distinct from the avian leukosis/sarcoma virus group (21), and are more closely related to mammalian retroviruses, both antigenically (2,47,48) and at the genome level (26,37). Nondefective strains of REV include REV-A, spleen necrosis virus (SNV), chicken syncytial virus (CSV), duck infectious anemia virus, and a number of other isolates (12). These nondefective REVs cause a runting disease syndrome, characterized by splenomegaly, necrosis of the spleen and liver, nerve lesions, and lymphomas of B cell or T cell type in chickens. A single replication-defective, acutely transforming REV isolate is known (REV-T), which carries the rel oncogene and which requires a nondefective helper virus (such as strain REV-A) for replication. REV-T causes an acute reticulum cell neoplasia in inoculated chickens. REVs are known to cause economically important immunodepression in infected chickens, and have been found as contaminants of Marek's disease (20,57) and fowlpox (5) vaccines. REV is associated with sporadic outbreaks of chronic neoplastic disease in turkeys and can cause significant losses in commercial turkey flocks (52,55).
Recombinant DNA technology has allowed the construction of recombinant vaccines that contain only those desired viral genes or gene products that induce immunity without exposing the animal to genes that may induce pathological disorders. Pox viruses, including Avipoxvirus, especially the fowlpox virus (FPV), provide excellent models for such vaccines. These viruses have a large DNA molecule with numerous non-essential regions that allow the insertion of several immunogenic genes into the same virus for the purpose of creating multivalent vaccines. These multivalent vaccines may induce cell-mediated as well as antibody-mediated immune response in a vaccinated host.
No vaccine for REV is currently available. Although accurate data on the economic significance of REV-associated diseases is not available, the oncogenic potential of these viruses, their ability to cause immunodepression, and their presence as contaminants in poultry biologics justifies research in this area and development of a suitable vaccine.
The envelope glycoproteins of retroviruses (encoded by the env genes) are known to be associated with virus neutralization. The various strains of REV are antigenically very similar (12), suggesting that a live vaccine expressing the env gene of a single REV isolate may provide protective immunity against numerous REV-associated diseases in poultry. The genomes of SNV and REV-A have been molecularly cloned (11,34). Sequence analysis of the env genes of these viruses shows that they are 92.7% identical to each other at the amino acid level, and about 40-50% identical to the env genes of type D and some type C simian retroviruses, with which they share a receptor (22,23).
The poxviruses, due to their high capacity for accepting foreign DNA and their cytoplasmic replication site, have attracted much attention in recent years as vectors for the expression of foreign genes, and for the construction of potential vaccines against animal diseases (6,40). Most of this attention has focused on vaccinia virus, the prototype of the genus Orthopoxvirus (19,27,30), because of its wide host range and relatively well defined molecular biology (18,29).
The Avipoxvirus genus has a host range which is restricted to avian species. Attenuated vaccine strains of these viruses are commercially available (46). Avipoxviruses show promise not only as safe vectors for the construction of live recombinant poultry vaccines, but also as vectors for replication-defective mammalian vaccines (42,43,45,50). Fowlpox virus (FPV), the prototype of this genus, has been used successfully as a recombinant vaccine to immunize chickens against several diseases, including Newcastle disease virus (7,8,17,25,36,41), avian influenza (4,9,44), Marek's disease virus (32,56), and infectious bursal disease virus (3).